The overall objectives of the project are total synthesis and elucidation of the chemistry of prostaglandin (PG) endoperoxide and thromboxane A molecules. PG endoperoxides possess an unusual bicyclic peroxide nucleus. They are a branch point in the oxidative transformation of polyunsaturated fatty acids into a vast array of physiologically active metabolites. The biological role of PG endoperoxides depends in large measure on enzymatic conversion into prostaglandins, thromboxane A, and prostacyclin. Our studies of the chemistry of the PG endoperoxide nucleus will guide parallel studies of PG endoperoxides themselves and eventually provide a basis for interpreting the biochemistry of these natural products. Fourrier transform NMR methods which we developed during the past year for monitoring rapid or dilute reactions will be exploited for studying catalyzed reactions of the PG endoperoxide nucleus. The mechanisms of reactions promoted by various amines will be characterized kinetically and thermodynamically, and other catalysts will be sought. Such studies are important for understanding enzymatic transformations of PG endoperoxides which are catalytic processes. Synthetic studies on the thromboxane A nucleus will be initiated and new approaches of PG endoperoxides will be examined.